Pancreatic ductal adenocarcinoma (PDAC) is challenging to treat – able to survive with limited blood supply and low oxygen, and with the ability to protect itself from the immune system, the disease causes few symptoms in its early stages. As a result, PDAC is often diagnosed when the disease is more advanced – and when the prognosis for patients tends to be bleak.
Earlier diagnosis is likely to translate to improved survival, so a team of researchers, including Cesar Castro, Assistant Professor of Medicine at Harvard Medical School, have developed a new diagnostic assay that performs better than the current blood test and has the potential to diagnose PDAC earlier. “No current blood-based laboratory test exists to reliably identify early PDAC without high rates of false positives, causing undue alarm for both patients and providers,” said Castro. “With reliable early detection methods, we would expect significant rather than incremental improvements for patient survival,” he added. The test uses nanotechnology to detect tumor-derived extracellular vesicles (tEVs) in plasma. These vesicles, which are structurally stable, relatively abundant, and have a biological makeup very similar to the main tumor, should be able to act as “serial peripheral windows” into PDAC tumors, without the need for tissue biopsy, according to Castro.
The tEVs are detecting using a plasmonic sensing system, in which the light emitted through gold nanopores is measured – the tEVs are bound via monoclonal antibodies immobilized on the surface of the pores, and this causes a spectral shift in the light that passes through the pores. After initially studying around 50 proteins, the team found that individual tEV markers didn’t appear to be accurate enough to be clinically useful in isolation. However, a panel of five tEVs produced an accuracy of 84 percent, a sensitivity of 86 percent and a specificity of 81 percent when differentiating PDAC from other pancreatic diseases (1). Analysis takes 10 minutes and costs US$60 per patient – $42 for the chip, and $18 for the cost of the antibodies. “Rather than seeking one universal, yet elusive PDAC marker that likely does not exist given human biological complexity, our work identified a multi-component PDAC signature with excellent diagnostic performance,” said Castro. Next, the team plans to demonstrate the real-world performance of the test, and look into its potential use for screening patients at high risk of developing PDAC.
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References
- KS Yang et al., “Multiparametric plasma EV profiling facilitates diagnosis of pancreatic malignancy”, Sci Transl Med, 9, eaal3226 (2017). PMID: 28539469.